Management of Metastatic Humeral Disease (2023)

Three lower quality studies were included and examined for this portion of the clinical practice guideline. These studies were retrospective and included low numbers of patients. Further, these studies included varied outcomes measured in terms of surgical complications and clinical function.  

When treating pathologic diaphyseal humerus fractures in the setting of metastatic disease, the available evidence does not appear to show a significant difference in clinical outcomes (pain relief, upper extremity function, complication rates) between these constructs.  However, with the low numbers available there was noted an increased failure rate with photodynamic polymer fixation compared to intramedullary nail fixation.  Despite this potential difference, there does not appear to be a significant difference in reoperation rate between plating/internal fixation, intramedullary fixation, and photodynamic polymer.

Based on the low-level evidence of the articles analyzed, any of the constructs, including intramedullary nailing, photodynamic polymer, or plating/internal fixation, constitutes a reasonable and safe option when treating realized or impending pathologic diaphyseal humerus fractures. However, caution is advised regarding the use of photodynamic polymer fixation until further evidence is available due to the potential higher failure rates with this construct. 

Further research is needed to better elucidate any potentially undetected outcome difference among the various constructs. The best study design to help determine this would be a collaborative, multicenter, randomized controlled trial.

No studies met inclusion criteria to compare en bloc resection and internal fixation in terms of disease control or clinical outcomes.  Based on the lack of definitive evidence, no recommendations can be made for or against specific surgical treatments for metastatic disease of the humerus.  While supporting literature is lacking, it is appropriate for the surgeon to consider en bloc resection based on the clinical circumstances and/or the reconstructive needs of the patient.  The histologic subtype of metastatic bone disease, oligometastatic disease state, condition of the adjacent joint, available bone stock, and other patient-centric factors may indicate resection as an appropriate treatment.  

Future studies should compare internal fixation versus intramedullary nailing versus en bloc resection for functional outcomes, failure and/or reoperation rates, pain relief, and oncologic outcomes.  Comparisons between histologic primaries and number of bony metastases should be considered in these studies.  

While specific literature is lacking, the group recommends that both nonoperative treatment and operative treatment can be considered based on the clinical circumstances of the patient, active comorbidities, metastatic disease burden and prognosis, location of the lesion, histologic subtype, presence of displacement or angulation, expected responsiveness to radiation and/or chemotherapy, and patient goals and expectations. 

Future research such as prospective cohort studies could help elucidate the clinical scenarios in which patients can be treated successfully with nonoperative management for metastatic disease of the humerus. 

A single small, retrospective comparison study demonstrated improved postoperative pain relief and functional outcomes at 1 and 6 weeks postoperatively with the addition of cement to intramedullary nailing of pathologic humeral shaft fractures.  These results were compared to a historical cohort of uncemented intramedullary nails.  There was no difference in perioperative complications, and no difference in pain or functional outcomes at 6 months postoperatively. 

Two other studies included in the review were also retrospective studies, one of which included 39 patients and the other 208 patients. These both appeared to include lesions at the proximal, diaphyseal, and distal humerus. In the larger study (excluding endoprosthetic reconstruction), plate fixation (as compared to intramedullary fixation), had a higher failure rate.  The other included study did not note a difference between these constructs.  

Future studies should compare cemented and cementless constructs for fixation of pathologic humerus fractures, and evaluate pain, location of the lesion, functional outcomes, and mechanical failure rates of each construct.  

Two retrospective comparative studies demonstrate a decreased rate of dislocation/subluxation, improved shoulder range-of-motion, and decreased reoperation rates with reverse total shoulder arthroplasty compared to hemiarthroplasty. One study demonstrated decreased local tumor recurrence in the reverse arthroplasty group as well. Careful consideration of anatomy involved in resection and harboring metastatic disease (glenoid, deltoid insertion/muscle, axillary nerve) as well as patient-centric factors should be used to guide appropriate selection of technique.

Future research should involve cohort or randomized studies between hemiarthroplasty and reverse total shoulder arthroplasty in comparable patient populations to evaluate range-of-motion, instability, reoperation rates, and pain between the two reconstructive techniques. 

There is a lack of data examining the socioeconomic impact of race, gender, and insurance status on the outcome of patients with non-primary malignancies. Current data is limited to small series of patients and a low-quality of evidence.  Similar to studies in other types of cancers, lack of insurance or having Medicaid, lower household income and black race were associated with a poor outcome. The studies reviewed showed rapidly growing histologies to be most often lung, gastrointestinal, and renal. The slower growing histologies were most often breast, prostate and thyroid. There were no studies describing the type of lesion (lytic vs blastic) as a predictor. There is likely no way to improve the quality of evidence for these studies as it would be near impossible to maintain equipoise while performing a prospective randomized study on this topic, however future studies on the use of prospectively collected data from multicenter or international collaborations may shed insight into the impact of these socioeconomic factors.

Both the American Society of Clinical Oncology and the American Society of Hematology (ASCO and ASH) guidelines recommend that patients with cancer without a history of VTE undergoing a major surgical procedure should be offered pharmacologic prophylaxis with either unfractionated heparin or low molecular weight heparin (LMWH), unless contraindicated because of active bleeding or high bleeding risk. The highest risk period for patients is in the perioperative setting in which they are hospitalized and immobilized.  

Recommendations from the International Consensus Meeting – Venous Thromboembolism (ICM-VTE) for Shoulder and Elbow state that VTE prophylaxis should be considered in patients undergoing osteosynthesis who are also at high risk of VTE, and those undergoing surgery under general anesthesia that lasts over 90 minutes. Regarding shoulder arthroplasty, in patients without substantial risk factors for VTE, they do not recommend LMWH or direct oral anticoagulants (DOAC). However, they do not comment on those with substantial risk factors for VTE. 

The ICM-VTE for Oncology states that all patients with bone metastases undergoing major surgical intervention should be offered pharmacologic thromboprophylaxis unless contraindicated. They state that larger studies are needed to determine optimal pharmacologic thromboprophylaxis between low molecular weight heparin, direct oral anticoagulants, vitamin K antagonists, and aspirin. These would include large, prospective, randomized studies conducted in collaboration with hematology and medical oncology specialists.